Abstract
BackgroundFormation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA.MethodsWe analyzed gene expression and clinical data of 30 PVAT around AAA and 30 PVAT around normal abdominal aorta (NAA). The diagnostic markers and immune cell infiltration of PVAT were further investigated by WGCNA, CIBERSORT, PPI, and multiple machine learning algorisms (including LASSO, RF, and SVM). Subsequently, eight-week-old C57BL/6 male mice (n = 10) were used to construct AAA models, and aorta samples were collected for molecular validation. Meanwhile, fifty-five peripheral venous blood samples from patients (AAA vs. normal: 40:15) in our hospital were used as an inhouse cohort to validate the diagnostic markers by qRT-PCR. The diagnostic efficacy of biomarkers was assessed by receiver operating characteristic (ROC) curve, area under the ROC (AUC), and concordance index (C-index).ResultsA total of 75 genes in the Grey60 module were identified by WGCNA. To select the genes most associated with PVAT in the grey60 module, three algorithms (including LASSO, RF, and SVM) and PPI were applied. EGR1 and KLF4 were identified as diagnostic markers of PVAT, with high accurate AUCs of 0.916, 0.926, and 0.948 (combined two markers). Additionally, the two biomarkers also displayed accurate diagnostic efficacy in the mice and inhouse cohorts, with AUCs and C-indexes all >0.8. Compared with the NAA group, PVAT around AAA was more abundant in multiple immune cell infiltration. Ultimately, the immune-related analysis revealed that EGR1 and KLF4 were associated with mast cells, T cells, and plasma cells.ConclusionEGR1 and KLF4 were diagnostic markers of PVAT around AAA and associated with multiple immune cells.
Highlights
Abdominal aortic aneurysm (AAA) is a pathological and progressive dilatation of the infrarenal abdominal aorta, which results in an increasing risk of rupture
The heatmap depicted topological overlap matrix (TOM) among 400 genes in Weighted gene coexpression network analysis (WGCNA) (Figure 3A), and the scatterplot displayed correlation between Perivascular adipose tissue (PVAT) and 75 genes in the grey60 module (Figure 3D)
(3) Through immune correlation analysis, we found that the upregulation of EGR1 and KLF4 promoted the proliferation of multiple immune cells, thereby promoting the expansion of abdominal aorta
Summary
Abdominal aortic aneurysm (AAA) is a pathological and progressive dilatation of the infrarenal abdominal aorta, which results in an increasing risk of rupture. Male sex, age older than 65 years, obesity, and positive family history are the major risk factors of AAA [2, 3]. During the AAA formation and progression, the three-layered vascular wall of the abdominal aorta gradually expands and weakens [4]. Inflammatory cell infiltration, oxidative stress, vascular smooth muscle cell (VSMC) depletion, and destructive extracellular matrix are the primary pathophysiology mechanism of AAA [5, 6]. Formation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
